Semiclassical Vibrational Spectroscopy of Biological Molecules Using Force Fields.
Semiclassical spectroscopy is a practical way to get an accurately approximate quantum description of spectral features starting from ab initio molecular dynamics simulations. The computational bottleneck for the method is represented by the cost of ab initio potential, gradient, and Hessian matrix estimates. This drawback is particularly severe for biological systems due to their unique complexity and large dimensionality. The main goal of this manuscript is to demonstrate that quantum dynamics and spectroscopy, at the level of semiclassical approximation, are doable even for sizable biological systems. To this end, we investigate the possibility of performing semiclassical spectroscopy simulations when ab initio calculations are replaced by computationally cheaper force field evaluations. Both polarizable (AMOEBABIO18) and nonpolarizable (AMBER14SB) force fields are tested. Calculations of some particular vibrational frequencies of four nucleosides, i.e., uridine, thymidine, deoxyguanosine, and adenosine, show that ab initio simulations are accurate and widely applicable. Conversely, simulations based on AMBER14SB are limited to harmonic approximations, but those relying on AMOEBABIO18 yield acceptable semiclassical values if the investigated conformation has been included in the force field parametrization. The main conclusion is that AMOEBABIO18 may provide a viable route to assist semiclassical spectroscopy in the study of large biological molecules for which an ab initio approach is not computationally affordable.


A randomized controlled trial of the effectiveness of a postnatal psychoeducation programme on self-efficacy, social support and postnatal depression among primiparas.
To examine the effectiveness of a postnatal psychoeducation programme in enhancing maternal self-efficacy and social support and reducing postnatal depression among primiparas. Primiparas experience various challenges during the early postnatal period with low self-efficacy, depression and lack of social support. Support in the form of postnatal educational programmes is needed to improve these outcomes of primiparas. A randomized controlled two-group pre-test-post-test design was adopted. Data were collected from June-December 2012 in a public hospital in Singapore from 122 primiparas, who were randomly assigned to the intervention (n = 61) or control group (n = 61). The intervention group received postnatal psychoeducation programme and routine care while the control group received routine care only. The Maternal Parental Self-Efficacy scale, Perinatal Infant Care Social Support scale and Edinburgh Postnatal Depression Scale were used to measure outcomes of maternal parental self-efficacy, social support and postnatal depression. The mean percentage changes of all three outcome variables from baseline to 6 and 12 weeks postpartum between groups were used when performing repeated measures multivariate analysis of covariance. The intervention group had significantly higher scores of maternal parental self-efficacy and social support and lower scores of postnatal depression at 6 and 12 weeks postpartum when compared with the control group. The postnatal psychoeducation programme was effective in improving maternal outcomes and hence could be introduced as routine care with ongoing evaluation in the postnatal period. Future studies could focus on the effects of this programme on other populations. ISRCTN15886353.


Cysteamine supplementation during in vitro maturation and embryo culture: a useful tool for increasing the efficiency of bovine in vitro embryo production.
Cysteamine when added during in vitro maturation (IVM) or in vitro embryo culture (IVC) stimulates glutathione (GSH) synthesis and improves embryo developmental rates. This suggests that GSH synthesis is decreased in the in vitro produced embryo. The present study was carried out to evaluate if addition of cysteamine to culture medium at the same time, during IVM and IVC of bovine oocytes, may promote an overall improvement on the developmental rate and embryo quality. Oocytes were matured in TCM 199 supplemented with 10% (v/v) fetal calf serum, hormones, and 0 or 100 microM of cysteamine for 24 hr. After IVM, the oocytes were fertilized (day 0). Day 2 embryos (2-8 cell) were washed and transferred to fresh IVC medium supplemented with 0, 25, 50, or 100 microM of cysteamine and cultured for 48 hr. After this, embryos were cultured in IVC medium without cysteamine until day 8 of IVC. In the present study, we confirmed our previous results by demonstrating that the percentage of embryos that developed to the blastocyst stage was significantly higher (P < 0.05) when 100 microM of cysteamine was added during IVM, and this was further improved when 100 and 50 microM of cysteamine where present during IVM and IVC, respectively (P < 0.05). After cryopreservation, no differences were observed on embryo development, but a significant increase on embryo hatching was found between unsupplemented and supplemented oocytes with 100 and 50 microM of cysteamine during IVM and IVC, respectively (P < 0.05). We can conclude that GSH synthesis stimulation during bovine IVM with cysteamine, concomitant with GSH stimulation during IVC, will be a useful and simple tool for increasing the efficiency of in vitro bovine embryo production.


Signaling-State Formation Mechanism of a BLUF Protein PapB from the Purple Bacterium Rhodopseudomonas palustris Studied by Femtosecond Time-Resolved Absorption Spectroscopy.
We studied the signaling-state formation of a BLUF (blue light using FAD) protein, PapB, from the purple bacterium Rhodopseudomonas palustris, using femtosecond time-resolved absorption spectroscopy. Upon photoexcitation of the dark state, FADH(•) (neutral flavin semiquinone FADH radical) was observed as the intermediate before the formation of the signaling state. The kinetic analysis based on singular value decomposition showed that FADH(•) mediates the signaling-state formation, showing that PapB is the second example of FADH(•)-mediated formation of the signaling state after Slr1694 (M. Gauden et al. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 10895-10900). The mechanism of the signaling-state formation is discussed on the basis of the comparison between femtosecond time-resolved absorption spectra of the dark state and those obtained by exciting the signaling state. FADH(•) was observed also with excitation of the signaling state, and surprisingly, the kinetics of FADH(•) was indistinguishable from the case of exciting the dark state. This result suggests that the hydrogen bond environment in the signaling state is realized before the formation of FADH(•) in the photocycle of PapB.


"I've Learned to Value Myself More": Piloting an Adapted Multilevel Intervention for Transgender Women Sex Workers Living with HIV in the Dominican Republic.
Purpose: Transgender (trans) women living with HIV experience suboptimal care and treatment outcomes. We adapted a multilevel intervention to improve HIV outcomes and overall well-being among trans women sex workers living with HIV. The intervention, called Abriendo Puertas (AP; Opening Doors), included: individual counseling, peer navigation, and community mobilization "open houses." The purpose of this article is to describe acceptability and initial outcomes of the adapted AP pilot and explore intervention experiences to inform recommendations for improvement. Methods: After an iterative adaptation process, we recruited 30 trans women sex workers living with HIV to participate in the pilot. We conducted baseline and endline (12-months) surveys to compare HIV care and treatment outcomes and qualitative interviews to assess intervention experiences with a subsample (n=20). Results: Intervention retention was high, with 86.7% of participants (n=26/30) completing both baseline and endline surveys. At endline, there was a significant increase in current anti-retroviral therapy (ART) use (70.0% to 84.6%, p<0.03) and positive, but not significant, trends in missed care appointments in the past 6 months (34.5% to 20.0%, p<0.39) and not having missed any ART doses in the past 4 days (85.7% to 95.5%, p<0.50). Intervention acceptability was high across all components: individual counseling (96.1%), peer navigation (80.8%), and open houses (84.6%). Participants emphasized that trust and being treated with respect allowed them to relax and improve their self-esteem. Limited trust and cohesion among trans women, however, limited more extensive engagement with peer navigation and community mobilization components. Conclusion: Future efforts to strengthen the AP intervention with trans women sex workers should continue to address emotional, instrumental, and informational support needs related to living with HIV through individual counseling, peer navigation, and open houses while also enhancing group-level activities to build trust and generate a collective commitment to promote the well-being of the community.


Analysis of the effects of COHb, lactate, and troponin levels on the clinical process and outcome in patients who were admitted to the emergency service due to carbon monoxide poisoning.
The aim of the present study was to determine the demographic, medical, and treatment characteristics of patients followed up with the diagnosis of carbon monoxide (CO) poisoning in emergency care and also to determine the relationship of these patients' clinical process and outcome between carboxyhemoglobin (COHb), lactate, and troponin levels. The present study was conducted retrospectively between 01/01/2013 and 01/01/2016 by examining 450 patients who were referred to the emergency service for CO poisoning. The ages; sexualities; manners of application; clinical findings; levels of blood COHb, lactate, and troponin; applied oxygen treatment method; and outcome of patients were evaluated. Data analysis was done by Shapiro-Wilk, Student's t, Mann-Whitney U, and chi-square tests. A total of 450 patients were included in the study. The median age of the patients was 35 (interquartile range (IQR) 26.75-45.00) years. In the study where data are not homogeneously distributed, the median levels of COHb, lactate, and troponin were 11.80% (IQR 3-23), 1.60 (IQR 1.10-2.5) mmol/l, and 0.00 (IQR 0.000-0.003) ng/ml, respectively. The levels of lactate were detected to be statistically high in patients who had syncope and who received hyperbaric oxygen treatment (p<0.05). In addition, the levels of lactate and troponin were significantly higher in patients who were hospitalized (p<0.05). The levels of COHb, lactate, and troponin can provide an insight to the clinician about hospitalization and the type of treatment.


Robust model fitting for the non linear structural equation model under normal theory.
Structural equation modelling has been widely applied in behavioural, educational, medical, social, and psychological research. The classical maximum likelihood estimate is vulnerable to outliers and non-normal data. In this paper, a robust estimation method for the nonlinear structural equation model is proposed. This method gives more weight to data that are likely to occur based on the structure of the posited model, and effectively downweights the influence of outliers. An algorithm is proposed to obtain the robust estimator. Asymptotic properties of the proposed method are investigated, which include the asymptotic distribution of the estimator, and some statistics for hypothesis testing. Results from a simulation study and a real data example show that our procedure is effective.


Autocatalytic activities of intron 5 of the cob gene of yeast mitochondria.
The terminal intron of the mitochondrial cob gene of Saccharomyces cerevisiae can undergo autocatalytic splicing in vitro. Efficient splicing of this intron required a high concentration of monovalent ion (1 M). We found that at a high salt concentration this intron was very active and performed many of the reactions described for other group I introns. The rate of the splicing reaction was dependent on the choice of the monovalent ion; the reaction intermediate, the intron-3' exon molecule, accumulated in NH4Cl but not in KCl. In addition, the intron was more reactive in KCl, accumulating in two different circular forms: one cyclized at the 5' intron boundary and the other at 236 nucleotides from the 5' end. These circular forms were able to undergo the opening and recyclization reactions previously described for the Tetrahymena rRNA intron. Cleavage of the 5' exon-intron boundary by the addition of GTP did not require the 3' terminus of the intron and the downstream exon. An anomalous guanosine addition at the 3' exon and at the middle of the intron was also detected. Hence, this intron, which requires a functional protein to splice in vivo, demonstrated a full spectrum of characteristic reactions in the absence of proteins.


Effects of quinidine on renal biochemistry and function in young and old rats.
Nephrotoxic effects of quinidine in male Fischer-344 rats in ages of 3-4 months and 20-22 months were evaluated. Renal cortical slice oxygen consumption, accumulation of p-aminohippurate and tetraethyl ammonium were inhibited in vitro. No age-related differences were observed. Quinidine decreased respiratory control index and ADP/O ratio in both age groups. Quinidine administration at 75 mg/kg/day for four days reduced tetraethylammonium transport in both young and old. Blood urea nitrogen increased in the old, but not in the young rats. Serum creatinine levels were elevated in both age groups. Renal cortical slice oxygen consumption decreased in the young but not in the old rats after quinidine administration. No changes in RCI or ADP/O ratio were observed in the two age groups. The results indicate that Fischer-344 rats in the ages of 20-22 months are not increasingly susceptible to quinidine-induced nephrotoxicity.


Use of mesenchymal stem cells seeded on the scaffold in articular cartilage repair.
Articular cartilage has poor capacity for repair. Once damaged, they degenerate, causing functional impairment of joints. Allogeneic cartilage transplantation has been performed for functional recovery of articular cartilage. However, there is only a limited amount of articular cartilage available for transplantation. Mesenchymal stem cells (MSCs) could be potentially suitable for local implantation. MSCs can differentiate into chondrocytes. Several studies have demonstrated the therapeutic potential of MSCs in the repair of articular cartilage in animal models of articular cartilage damage and in patients with damaged articular cartilage. To boost post-implantation MSC differentiation into chondrocytes, the alternative delivery methods by scaffolds, using hyaluronic acid (HA) or poly-lactic-co-glycolic-acid (PLGA), have developed. In this review, we report recent data on the repair of articular cartilage and discuss future developments.


Association between FTO, MC4R, SLC30A8, and KCNQ1 gene variants and type 2 diabetes in Saudi population.
Recent genome wide association studies identified many loci in several genes that have been consistently associated with type 2 diabetes mellitus in various ethnic populations. Among the genes that were most strongly associated with diabetes were fat mass- and obesity-associated, melanocortin 4 receptor, solute carrier family 30 member 8 (SLC30A8), and a member of the potassium voltage-gated channels. In the present study, we examined the association between variants in fat mass- and obesity-associated [rs9939609 (A/T)], melanocortin 4 receptor [rs17782313 (C/T), and rs12970134 (A/G)], SLC30A8 [rs13266634 (C/T)], and a member of the potassium voltage-gated channels [rs2237892(C/T)] genes in diabetes patients from Saudi Arabia. Genotypes were determined using the TaqMan single-nucleotide polymorphism genotype analysis technique. Minor allele frequency of the 4 variants tested was comparable between type 2 diabetes cases and controls. We observed an association between allele variants of SLC30A8 [rs13266634 (C/T)] and type 2-diabetes (P = 0.04). The other single-nucleotide polymorphisms examined in this study showed moderate or no correlation with diabetes in Saudis. Our data indicate that the SLC30A8 polymorphisms are associated with type 2 diabetes in the Saudi population. There is no evidence supporting an association between variants in the fat mass- and obesity-associated and melanocortin 4 receptor, and a member of the potassium voltage-gated channels genes and type 2 diabetes in the Saudi population.


[Effect of cyclic-tension force on the expression of osteogenesis genes in human periodontal ligament cells].
To investigate the effect of cyclic-tension force on the expression of osteogenesis genes in human periodontal ligament cells (HPDLC). HPDLC were cultured on flexible-bottomed plates and subjected to 12% elongation by strain unit at 6 cycles/min (i.e.5-s elongation and 5-s relaxation) for 48 hours in the experimental groups. GEArray Q series Human Osteogenesis Gene Array was used to identify the genes expressed in HPDLC, including growth factors and associated molecules, extracellular matrix and its associated proteins, cell adhesion molecules and housekeeping genes. The changes in the expression of 96 representative transcripts were determined by arrayed cDNA hybridization. After application of tension force, 21 genes were significantly upregulated, including 10 growth factors and associated molecules, 10 extracellular matrix and its associated protein and 1 cell adhesion molecules. Two genes were significantly downregulated, including 1 growth factors and associated molecules and 1 cell adhesion molecules. The HPDLC can differentiate into osteoblast-like cells by mechanical stretch induction through the activation of some osteogenesis genes.


Ambulatory surgery for chronic venous insufficiency using radiofrequency thermoablation: quality and satisfaction.
Chronic venous disease is a frequent and prevalent pathology. Its surgical treatment has been shown to be cost-effective. Thermal endoablation performed as major outpatient surgery (MAS) is the technique of choice. To know the satisfaction of patients after MAS and the quality of care provided. Observational, descriptive, cross-sectional study, carried out between January 2019 and March 2020. A survey was carried out on patients who underwent endovascular radiofrequency thermoablation in two hospitals in Spain, consisting of two questionnaires: one ad hoc and one another of satisfaction (SERCAL). Quality indices for MAS were measured. We analyzed 156 episodes. 145 interventions were carried out. We found 4 (2.8%) unscheduled admissions. 3 patients (2.1%) attended the emergency department. There was a 99.3% success rate. 100% of the patients had pre-surgical recommendations and informed consent. We obtained 48 surveys (response rate: 33.1%). All the patients gave a rating greater ≥ 8 in quality of care (x = 9.83) and would recommend this procedure to their relatives (x = 9.71). Endovascular radiofrequency thermoablation performed in MAS has a high success rate and a very low rate of admission and visit to the emergency room. Patient satisfaction is high.


Validation of different commercially available cholinesterases for pesticide toxicity test.
A systematic study of different commercially available cholinesterases (AChEs from electric eel, human erythrocytes, bovine erythrocytes and BuChE from horse serum) for the FIA determination of some frequently used organophosphate (paraoxon, oxydemeton-methyl, triazophos, diazionon) and carbamate (carbofuran, propoxur) pesticides was carried out. Responses of the previously developed photothermal FIA system were found to be dependent on the origin of cholinesterases and properties of tested pesticides. The highest sensitivity was obtained with electric eel AChE and the lowest sensitivity with horse serum BuChE. The LOD values for investigated pesticides correlate with acute toxicities expressed as LD50 (oral, rat). The presented FIA system could serve as an alternative screening test to evaluate the toxicity of different environmental samples, new cholinesterase inhibiting pesticides or other products (e.g. nerve gases).


High pressure study on molecular mobility of leucrose.
Broadband dielectric measurements on leucrose were performed under ambient and high pressure. We showed that in this disaccharide, there are two secondary relaxation modes, a slower one sensitive to pressure and a faster one that is not. This finding clearly indicates that the faster secondary relaxation originates from the intramolecular motion. This conclusion contradicted previous interpretations of this mode observed for trehalose and maltitol, systems very closely related to leucrose. In addition, pressure sensitivity of the slower relaxation confirms our recent interpretation about the character of this process. Furthermore, we discovered that unlike the faster relaxation, the slower secondary relaxation is sensitive to the thermodynamic history of measurements. Finally, monitoring the changes in maximum loss of the slower secondary relaxation measured at the same pressure and temperature conditions for glasses obtained via different thermodynamic routes enabled us to draw a conclusion about the density of the formed glasses. Our observations may be helpful in establishing a new method of suppressing crystallization of amorphous drugs.


The hypocretins: setting the arousal threshold.
Over a short period in the late 1990s, three groups converged on the discovery of a neuropeptide system, centred in the dorsolateral hypothalamus, that regulates arousal states, influences feeding and is implicated in the sleep disorder narcolepsy. Subsequent studies have illuminated many aspects of the circuitry of the hypocretin (also called orexin) system, which also influences hormone secretion and autonomic homeostasis, and have led to the hypothesis that most human narcolepsies result from an autoimmune attack against the hypocretin-producing neurons. The biochemical, physiological and anatomical components that regulate the switch between waking and sleeping are becoming clear. The rapidity with which the hypocretin story has emerged is a testament to both the conceptual and the technical evolution of genomic science in the past two decades.


Pressure-volume curves in smokers. Comparison with alpha-1-antitrypsin deficiency.
The diagnosis of emphysema has been associated with changes in the appearance of the pressure-volume (P-V) curve: reduced maximal recoil pressure, increased lung volume, and a shift in the position of the curve to the left. In our clinical practice, we have observed that patients with chronic obstructive lung disease (COPD) commonly had P-V curves with reduced maximal elastic recoil that are difficult to classify according to the classic description of the P-V curve in emphysema. In order to study the variability of P-V curves, we studied 39 cigarette smokers attending a pulmonary clinic (age, 61 +/- 1 yr; smoking history, 45 +/- 3 pack-years; mean +/- SEM) and compared them with 20 patients with alpha-1-antitrypsin deficiency (AATD) (age, 41 +/- 2 yr; 13 smokers with a smoking history of 17 +/- 2 pack-years, and seven nonsmokers). Subjects underwent spirometry, lung volume, and diffusing capacity measurements as well as static deflation P-V curves. To characterize the P-V curves, we used transpulmonary pressure at 90% of TLC (PL90) as a measure of overall recoil and specific compliance (Csp) as a measure of the slope of the initial part of the P-V curve. The curves of non-AATD smokers were classified into three groups: 13 had PL90 greater than or equal to 80% predicted (Group I), 13 had PL90 less than 80% predicted and Csp greater than or equal to 0.08 (Group II), and 13 had PL90 less than 80% predicted and Csp less than 0.08 (Group III).(ABSTRACT TRUNCATED AT 250 WORDS)


Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A retrospective cohort study.
Fungal Endocarditis (FE), a relatively rare disease, has a high rate of mortality and is associated with multiple morbidities. Aspergillus endocarditis (AE) is severe form of FE. Incidence of AE has increased and is expected to rise due to an increased frequency of invasive procedures, cardiac devices and prosthetic valves together with increased use of immune system suppressors. AE lacks most of the clinical criteria used to diagnose infective endocarditis (IE), where blood culture is almost always negative, and fever may be absent. Diagnosis is usually late and in many cases is made post-mortem. Late or mistaken diagnosis of AE contribute to delayed and incorrect management of patients. In the current study we aimed to describe the clinical, laboratory and imaging characteristics of AE, to identify predictors of early diagnosis of this serious infection. Patients with definite/possible IE, as diagnosed by the Kasr Al-Ainy IE Working Group from February 2005 through June 2016, were reviewed in this study. We compared the demographic, clinical, laboratory and imaging criteria of AE patients to non-fungal IE patients. This study included 374 patients with IE in which FE accounted for 43 cases. Aspergillus was the most common fungus (31 patients; 8.3%) in the patient group. Lack of fever and acute limb ischemia at presentation were significantly associated with AE (p < 0.001, p = 0.014, respectively). Health care associated endocarditis (HAE) and prosthetic valve endocarditis (PVE) were the only significant risk factors associated with AE (p < 0.001 for each). Mitral, non-valvular, and aortotomy site vegetations, as well as aortic abscess/pseudoaneurysm, were significantly associated with AE (p = 0.022, p = 0.004, p < 0.001, and p < 0.001, respectively). Through multivariate regression analysis, HAE, PVE, aortic abscess/pseudoaneurysm, and lack of fever were strongly linked to AE. The probability of an IE patient having AE with HAE, PVE, and aortic abscess/pseudoaneurysm, but no fever, was 0.92. In contrast, the probability of an IE patient having AE with fever, native valve IE, but no health-care associated IE and no abscess/pseudoaneurysm, was 0.003. Severe sepsis and mortality in the Aspergillus group were higher as compared to the non-fungal group (p = 0.098 and 0.097, respectively). Thirteen AE patients died during hospitalization. PVE, the use of single versus dual antifungal agents, severe heart failure, and severe sepsis were significant predictors of mortality (p = 0.008, 0.012, 0.003, and 0.01, respectively). To our knowledge, this is the first study to address diagnostic criteria for AE. Through multivariate regression analysis, absence of fever, HAE, PVE, and aortic abscess/pseudoaneurysm were strong predictors of AE. Use of these criteria my lead to earlier diagnoses of AE. Early treatment of AE patients with voriconazole in combination with other antifungal agents may be possible based on the previously mentioned criteria, which may facilitate better patient outcomes.


SAP and XIAP deficiency in hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is a multisystem inflammatory disorder due to cytokine overproduction from excessively activated lymphocytes and macrophages. HLH has been divided into two subgroups: primary HLH and secondary HLH. Primary HLH includes PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, SH2D1A and XIAP gene mutations; and secondary HLH is associated with infections, malignancies and autoimmune diseases. Among primary HLH-related genes, SH2D1A and XIAP are genetically responsible for X-linked lymphoproliferative syndrome (XLP) due to signaling-lymphocytic-activation-molecule-associated protein (SAP) and XIAP deficiencies, respectively. XLP is characterized by extreme vulnerability to Epstein-Barr virus infection. The major clinical manifestations of XLP consist of HLH (60%), lymphoproliferative disorder (30%) and dysgammaglobulinemia (30%). Analysis of clinical phenotypes of XLP patients suggests that XLP predominantly shows familial HLH phenotypes, whereas some XLP patients present sporadic HLH. For many decades, clinicians and investigators have been concerned with possible XLP in young boys presenting with Epstein-Barr-virus-associated HLH. This review aims to describe the new knowledge about XLP and to draw the attention of the pediatrician to XLP, which should be differentiated from other forms of HLH.


Screening of Endophytic Antagonistic Bacterium from Phellodendron amurense and Their Biocontrol Effects against Canker Rot.
Thirty-four strains of bacteria were isolated from Phellodendron amurense. Using Nectria haematococca as an indicator strain, the best strain, B18, was obtained by the growth rate method. The morphological, physiological and biochemical characteristics of strain B18 and its 16S DNA gene sequence were identified, and the biocontrol effect of strain B18 was assessed in pot and field tests, as well as in a field-control test. Drilling methods were used to determine the antibacterial activity of metabolites from strain B18 and their effects on the growth of pathogen mycelia and spores. The best bacteriostatic rate was 85.4%. B18 can hydrolyse starch and oxidize glucose but does not produce gas; a positive result was obtained in a gelatine liquefaction test. According to 16S DNA gene sequencing, strain B18 is Bacillus methylotrophicus (GenBank accession number: MG457759). The results of pot and field-control trials showed 98% disease control when inoculating 108 cfu/ml of the strain. The disease control effect of the B18 culture liquid (concentrations of 108, 2 × 106, 106, 5 × 105 and 2.5 × 105 cfu/ml) in the field-control test was higher than 80%, and the cure rate of the original delivery solution was 96%. Therefore, in the practical forestry production, a 2.5 × 105 cfu/ml culture liquidshould be applied in advance to achieve good control effects.


Anomalous fluctuations of renewal-reward processes with heavy-tailed distributions.
For renewal-reward processes with a power-law decaying waiting time distribution, anomalously large probabilities are assigned to atypical values of the asymptotic processes. Previous works have revealed that this anomalous scaling causes a singularity in the corresponding large deviation function. In order to further understand this problem, we study in this article the scaling of variance in several renewal-reward processes: counting processes with two different power-law decaying waiting time distributions and a Knudsen gas (a heat conduction model). Through analytical and numerical analyses of these models, we find that the variances show an anomalous scaling when the exponent of the power law is -3. For a counting process with the power-law exponent smaller than -3, this anomalous scaling does not take place: this indicates that if we only consider the standard deviation from the expectation, any anomalous behavior will not be detected. In this case, we argue that anomalous scaling appears in higher order cumulants. Finally, many-body particles interacting through soft-core interactions with the boundary conditions employed in the Knudsen gas are studied using numerical simulations. We observe that the variance scaling becomes normal even though the power-law exponent in the boundary conditions is -3.


Hormonal Effects of an Enzymatically Hydrolyzed Animal Protein-Based Biostimulant (Pepton) in Water-Stressed Tomato Plants.
Biostimulants may promote growth or alleviate the negative effects of abiotic stress on plant growth eventually resulting in enhanced yields. We examined the mechanism of action of an enzymatically hydrolyzed animal protein-based biostimulant (Pepton), which has previously been shown to benefit growth and yield in several horticultural crops, particularly under stressful conditions. Tomato plants were exposed to well-watered and water-stressed conditions in a greenhouse and the hormonal profiling of leaves was measured during and after the application of Pepton. Results showed that the Pepton application benefited antioxidant protection and exerted a major hormonal effect in leaves of water-stressed tomatoes by increasing the endogenous content of indole-3-acetic acid (auxin), trans-zeatin (cytokinin), and jasmonic acid. The enhanced jasmonic acid content may have contributed to an increased production of tocochromanols because plastochromanol-8 concentration per unit of chlorophyll was higher in Pepton-treated plants compared to controls. In conclusion, the tested Pepton application may exert a positive effect on hormonal balance and the antioxidant system of plants under water stress in an economically important crop, such as tomato plants.


Comparison of the Cobas 4800 HPV and HPV 9G DNA Chip Tests for Detection of High-Risk Human Papillomavirus in Cervical Specimens of Women with Consecutive Positive HPV Tests But Negative Pap Smears.
Detecting high-risk (HR) HPV is important for clinical management of women with persistent HPV-positive and Pap-negative results. The Cobas 4800 HPV test is the first FDA-approved HPV DNA test that can be used alone as a first-line screening tool. The HPV 9G DNA chip test is a PCR-based DNA microarray assay. We evaluated the patients of consecutive HPV-positivity on HPV 9G DNA chip test without cytologic abnormalities. We then compared the performances of HPV 9G DNA chip and the Cobas 4800 HPV tests for detecting HR HPV with each other and confirmed HPV genotyping using direct sequencing. All 214 liquid-based cytology specimens were collected from 100 women with consecutive HPV-positive and Pap-negative results on the HPV 9G DNA chip test between May 2012 and Dec 2013, but only 180 specimens were available for comparing HPV test results. The HPV 9G DNA chip and the Cobas 4800 HPV tests agreed with each other in 81.7% of the samples, and the concordance rate was greater than 97.2% for detecting HPV-16 or -18. For HR genotypes other than HPV types 16 and 18, the two tests agreed for 81.1% of the samples. The sensitivity of both assays for detecting HR HPV was 100%, regardless of HR genotypes. The HPV 9G DNA chip test may be as effective as the Cobas 4800 HPV test in detecting HR HPV, and has a similar ability to identify HPV-16 and -18.


Histological and immunohistological study of cryopreserved aortic valve grafts: the possibility of a clinical application for cryopreserved aortic valve xenograft.
The influence of preservation techniques on xenogeneic immune responses was examined to investigate the possibility of their clinical use. Mongrel dogs and pigs were used as allogeneic and discordant xenogeneic donors of aortic valve grafts, respectively. The allografts and xenografts were implanted in the abdominal aorta of mongrel dogs after cryopreservation or after fresh preservation. Allografts and xenografts were explanted at Days 7 and 42 for histological and immunohistochemical examination. In the fresh preserved allografts and the fresh preserved xenografts, the media of aortic wall grafts were significantly acellular at 7 days. Significant aortic medial destruction and neointimal proliferation with significant destruction of the valve leaflets was observed at 42 days. However, no differences were found among the preservation techniques in the xenogeneic grafts. To alleviate the lack of homografts, approaches such as the tissue-engineered graft may become an alternative in patients who are acceptable candidates.


[Rapid startup and nitrogen removal characteristic of anaerobic ammonium oxidation reactor in packed bed biofilm reactor with suspended carrier].
Packed bed biofilm reactor with suspended carrier was used to cultivate ANAMMOX bacteria with sludge inoculums from WWTP secondary settler. The startup of ANAMMOX reactor was comparatively studied using high nitrogen loading method and low nitrogen loading method with aerobically biofilmed on the carrier, and the nitrogen removal characteristic was further investigated. The results showed that the reactor could be started up successfully within 90 days using low nitrogen loading method, the removal efficiencies of ammonium and nitrite were nearly 100% and the TN removal efficiencywas over 75% , however, the high nitrogen loading method was proved unsuccessfully for startup of ANAMMOX reactor probably because of the inhibition effect of high concentration of ammonium and nitrite. The pH value of effluent was slightly higher than the influent and the pH value can be used as an indicator for the process of ANAMMOX reaction. The packed bed ANAMMOX reactor with suspended carrier showed good characteristics of high nitrogen loading and high removal efficiency, 100% of removal efficiency could be achieved when the influent ammonium and nitrite concentration was lower than 800 mg/L.


Coronary perforation complicating percutaneous coronary intervention in patients presenting with an acute coronary syndrome: An analysis of 1013 perforation cases from the British Cardiovascular Intervention Society database.
The evidence base for coronary perforation occurring during percutaneous coronary intervention in patients presenting with an acute coronary syndrome (ACS-PCI) is limited and the specific role of acute pharmacology in its clinical presentation unclear. Using the BCIS PCI database, data were analysed on all ACS-PCI procedures performed in England and Wales between 2007 and 2014. Multiple regressions were used to identify predictors of coronary perforation and its association with outcomes. Propensity score matching was used to evaluate the association between differing P2Y12 inhibitors or glycoprotein inhibitors (GPI) and CP. During 270,329 ACS-PCI procedures, 1013 coronary perforations were recorded (0.37%) with a stable annual incidence. In multiple regression analysis, covariates associated with increased frequency of coronary perforation included age, female gender, CTO intervention, number and length of stents used, and rotational atherectomy use, whilst differing P2Y12 inhibitors were not predictive. Using propensity score matching, use of a GPI was independently associated with tamponade (OR 1.50, [1.08-2.06], p = 0.014). The adjusted odds ratios for all clinical outcomes were adversely affected by coronary perforation. Coronary perforation is an infrequent event during ACS-PCI but is closely associated with adverse clinical outcomes. GPI use was associated with higher rates of tamponade.


Na+ / H+ exchanger-3 is involved in mouse blastocyst formation.
The mouse blastocyst consists of the trophectoderm, the inner cell mass, and a fluid-filled cavity, the blastocoel. Formation and subsequent expansion of this cavity is important for further differentiation of the inner cell mass and successful implantation. Previous work provided evidence that vectorial transport of Na+ and CL- ions through the trophectoderm into the blastocoel generates an osmotic gradient that drives fluid across this epithelium. As the activity of the Na+ / H+ exchanger (NHE) has been implicated as the exchanger responsible for facilitating the transtrophectodermal Na+ flux, the functional role of NHE in mouse blastocoel development was determined. Embryos were cultured in the presence of subtype-specific NHE inhibitors to examine the role of NHEs in blastocoel development. When 2-cell stage embryos were treated continuously with a specific inhibitor of NHE-1, cariporide, the embryos passed beyond the 8-cell stage and became blastocysts. However, in the presence of a specific inhibitor of NHE-3, S3226, the 2-cell stage embryos developed to the morula stage but formation of the blastocyst were inhibited in a dose-dependent manner. Cariporide did not inhibit the formation of the blastocoel cavity from the morula stage whereas S3226 did inhibit that process. S3226 also reduced the rate of re-expansion of blastocysts collapsed by cytochalasin D upon transfer to the control medium. An immunofluorescence study showed that NHE-3 was detected in the vicinity of the cell membrane of the trophectoderm, especially in the apical cell margins of the trophectoderm. These results suggest that NHE-3 is likely involved in blastocyst formation.


Evaluating the Diagnostic Performance of Prehospital Stroke Scales Across the Range of Deficit Severity: Analysis of the Prehospital Triage of Patients With Suspected Stroke Study.
The usefulness of prehospital scales for identifying anterior circulation large vessel occlusion (aLVO) in patients with suspected stroke may vary depending on the severity of their presentation. The performance of these scales across the spectrum of deficit severity is unclear. The aim of this study was to evaluate the diagnostic performance of 8 prehospital scales for identifying aLVO across the spectrum of deficit severity. We used data from the PRESTO study (Prehospital Triage of Patients With Suspected Stroke Symptoms), a prospective observational study comparing prehospital stroke scales in detecting aLVO in suspected stroke patients. We used the National Institutes of Health Stroke Scale (NIHSS) score, assessed in-hospital, as a proxy for the Clinical Global Impression of stroke severity during prehospital assessment by paramedics. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and the difference in aLVO probabilities with a positive or negative prehospital scale test (ΔPaLVO) for each scale for mild (NIHSS 0-4), intermediate (NIHSS 5-9), moderate (NIHSS 10-14), and severe deficits (NIHSS≥15). Among 1033 patients with suspected stroke, 119 (11.5%) had an aLVO, of whom 19 (16.0%) had mild, 25 (21.0%) had intermediate, 30 (25.2%) had moderate, and 45 (37.8%) had severe deficits. The scales had low sensitivity and positive predictive value in patients with mild-intermediate deficits, and poor specificity, negative predictive value, and accuracy with moderate-severe deficits. Positive results achieved the highest ΔPaLVO in patients with mild deficits. Negative results achieved the highest ΔPaLVO with severe deficits, but the probability of aLVO with a negative result in the severe range was higher than with a positive test in the mild range. Commonly-used prehospital stroke scales show variable performance across the range of deficit severity. Probability of aLVO remains high with a negative test in severely affected patients. Studies reporting prehospital stroke scale performance should be appraised in the context of the NIHSS distribution of their samples.


Pulmonary Parenchymal Lymphoma Diagnosed by Bronchoscopic Cryoprobe Lung Biopsy.
A 51-year-old man presented with progressively worsening lung infiltrates and respiratory failure. Extensive investigations including bronchoscopy with bronchoalveolar lavage and conventional transbronchial forceps biopsies failed to establish the diagnosis. After transfer to our institution, he underwent repeat bronchoscopy with transbronchial cryobiopsy, which provided large, high-quality biopsy specimens establishing the diagnosis of parenchymal diffuse large B-cell lymphoma.


Protein supplementation does not alter intramuscular anabolic signaling or endocrine response after resistance exercise in trained men.
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway appears to be the primary regulator of muscle protein synthesis. A variety of stimuli including resistance exercise, amino acids, and hormonal signals activate mTORC1 signaling. The purpose of this study was to investigate the effect of a protein supplement on mTORC1 signaling following a resistance exercise protocol designed to promote elevations in circulating hormone concentrations. We hypothesized that the protein supplement would augment the intramuscular anabolic signaling response. Ten resistance-trained men (age, 24.7 ± 3.4 years; weight, 90.1 ± 11.3 kg; height, 176.0 ± 4.9 cm) received either a placebo or a supplement containing 20 g protein, 6 g carbohydrates, and 1 g fat after high-volume, short-rest lower-body resistance exercise. Blood samples were obtained at baseline, immediately, 30 minutes, 1 hour, 2 hours, and 5 hours after exercise. Fine-needle muscle biopsies were completed at baseline, 1 hour, and 5 hours after exercise. Myoglobin, lactate dehydrogenase, and lactate concentrations were significantly elevated after resistance exercise (P < .0001); however, no differences were observed between trials. Resistance exercise also elicited a significant insulin, growth hormone, and cortisol response (P < .01); however, no differences were observed between trials for insulin-like growth factor-1, insulin, testosterone, growth hormone, or cortisol. Intramuscular anabolic signaling analysis revealed significant elevations in RPS6 phosphorylation after resistance exercise (P = .001); however, no differences were observed between trials for signaling proteins including Akt, mTOR, p70S6k, and RPS6. The endocrine response and phosphorylation status of signaling proteins within the mTORC1 pathway did not appear to be altered by ingestion of supplement after resistance exercise in resistance-trained men.


Uterine leiomyoma causing urinary obstruction of the transplanted kidney.
Obstruction of the ureter as a cause of acute or chronic kidney injury in the transplanted kidney is unusual beyond the perioperative period. We present a case of ureteric obstruction, infection and septicemia caused by a large uterine leiomyoma in a patient 8 years post transplantation. Initial treatment comprised of intravenous fluid and antibiotics followed by urgent drainage of the collecting system. Subsequent hysterectomy resolved the obstruction with resolution of renal failure. In young female kidney transplant recipients, gynecologic causes, although rare, need to be considered as possible etiologies of urinary obstruction and renal dysfunction.


A rare complication of tracheal intubation.
Accidental endobronchial intubation is a frequent complication in critically ill patients requiring tracheal intubation (TI). If such complication occurs, it is more often the right main bronchus that is intubated due to anatomical reasons. Left main bronchus (LMB) intubation is rare. Here, we report a case with auscultatory, bronchoscopic, and radiographic evidence of accidental LMB intubation in a pregnant woman with dengue shock syndrome. We highlight this case to increase awareness about this possible-but-rare complication of TI.


Recommendations for the evaluation of aromatic stabilization energies.
[reaction: see text] Perturbing influences, such as strain and the presence of heteroatoms, complicate the evaluation of aromatic stabilization energies (ASE). These complications are overcome easily by employing the "isomerization method". This is based on the differences (ISE) between total energies computed for only two species: a methyl derivative of the aromatic system and its nonaromatic exocyclic methylene isomer. The ISEs of benzene, pyridine, and naphthalene as well as the strained [5]paracyclophane, methano[10]annulene, and octadehydro[14]annulene are evaluated.


Prevalence of cardiovascular risk factors in schoolchildren from a rural and urban area in Colombia
Introduction: Cardiovascular risk factors (CVRF) have their origin in childhood. Several studies have shown differences in the prevalence of CVRFs between rural and urban areas, probably related to lifestyle behaviors. Objective: To describe the CVRFs identified in children from a rural and urban population in Colombia. Materials and methods: A cross-sectional study was conducted between March and June 2013 in schoolchildren from an urban and a rural area in Colombia. Weight, height, blood pressure, triglycerides, fasting glucose, and total cholesterol were measured, and a survey covering nutrition, physical activity, and passive smoking was applied. The prevalence of CVRFs was calculated with a 95% CI. Results: A total of 1,055 schoolchildren (833 urban, 222 rural) participated; their mean age was 6.71 years. The prevalence of CVRFs in the rural and the urban study population, respectively, was 68.69%/90.16% for sedentary lifestyle, 97.18%/95.44% for unhealthy diet, 11.16%/14.52% for passive smoking, 0%/5.64% for obesity, 6.31%/11.28% for hypertension, 0%/0% for diabetes, and 18.28%/16.31% for total cholesterol. A total of 99.15% of the study population had at least one CVRF, with an average of 3.14 for the urban area (SD:1.12), and of 2.76 for the rural one (SD: 1.1). Overweight children had a higher prevalence of hypertension (15.21%; 95% CI:11.04%-20.59%) and sedentary lifestyle (90.69%), compared to those without this risk factor (8.98% and 84.32%, respectively). Conclusions: Our results showed a high prevalence of CVRFs in children, especially in the urban area. Public health strategies adapted to the rural and urban populations should be implemented.


Immunogenetics of human IgE.
Immunoglobulin E plays a central role in mediating the pathology of allergic disease. Conversely, it is involved in the normal protective immune responses against parasite infection. Both these biological processes depend on interaction between the variable regions (VH and VL) of IgE antibodies and target antigen. It is now feasible to investigate the molecular nature of VH regions used to encode IgE at the genetic level. Using this technology to analyze IgE in patients with asthma has revealed features which may have relevance for allergic disease. First, preferential choice of VH genes, with dominance of the small VH5 family, particularly the VH32 gene, has been found. This may implicate a B cell superantigen (superallergen) selectively driving the use of these genes. Second, VH5 genes in IgE are somatically mutated with clear hot spots of mutational activity. Mutational hotspots, which are a feature of the VH5 gene, are supplemented in IgE by ongoing mutations which may be involved in affinity maturation. Third, a single B cell can switch to either IgE or IgG4, with both variants coexisting in blood. These findings may provide clues to the mechanism by which IgE is generated, and suggest options for therapeutic intervention.


KOSMOS: a universal morph server for nucleic acids, proteins and their complexes.
KOSMOS is the first online morph server to be able to address the structural dynamics of DNA/RNA, proteins and even their complexes, such as ribosomes. The key functions of KOSMOS are the harmonic and anharmonic analyses of macromolecules. In the harmonic analysis, normal mode analysis (NMA) based on an elastic network model (ENM) is performed, yielding vibrational modes and B-factor calculations, which provide insight into the potential biological functions of macromolecules based on their structural features. Anharmonic analysis involving elastic network interpolation (ENI) is used to generate plausible transition pathways between two given conformations by optimizing a topology-oriented cost function that guarantees a smooth transition without steric clashes. The quality of the computed pathways is evaluated based on their various facets, including topology, energy cost and compatibility with the NMA results. There are also two unique features of KOSMOS that distinguish it from other morph servers: (i) the versatility in the coarse-graining methods and (ii) the various connection rules in the ENM. The models enable us to analyze macromolecular dynamics with the maximum degrees of freedom by combining a variety of ENMs from full-atom to coarse-grained, backbone and hybrid models with one connection rule, such as distance-cutoff, number-cutoff or chemical-cutoff. KOSMOS is available at http://bioengineering.skku.ac.kr/kosmos.


Using social determinants of health to link health workforce diversity, care quality and access, and health disparities to achieve health equity in nursing.
It is widely accepted that diversifying the nation's health-care workforce is a necessary strategy to increase access to quality health care for all populations, reduce health disparities, and achieve health equity. In this article, we present a conceptual model that utilizes the social determinants of health framework to link nursing workforce diversity and care quality and access to two critical population health indicators-health disparities and health equity. Our proposed model suggests that a diverse nursing workforce can provide increased access to quality health care and health resources for all populations, and is a necessary precursor to reduce health disparities and achieve health equity. With this conceptual model as a foundation, we aim to stimulate the conceptual and analytical work-both within and outside the nursing field-that is necessary to answer these important but largely unanswered questions.


[Misleading diagnosis of a migratory epigastric pain in mobile emergency units: spontaneous rupture of the oesophagus].
The local mobile emergency unit took charge of a patient who suffered from a sudden migratory epigastric pain in the back. The clinical picture led to an initial diagnosis of an aorta dissection. Admitted to Grenoble UH's emergency unit, the radiological examination ruled out a cardiovascular pathology. Emergency surgery, performed only a few hours after the symptoms began, allowed to correctly diagnose a spontaneous rupture of the oesophagus. Fast and specialised medical treatment avoided the risk of an unfavourable development of the Boerhaave's syndrome. It is essential that mobile emergency units personnel are made aware of this rare pathology, even though it remains particularly difficult to diagnose due to its rather non-specific symptoms.


The post-concussional syndrome then and now.
The post-concussional syndrome (PCS) is a relatively common and potentially devastating condition. It may follow what seem to be quite trivial closed head injuries, as well as more obviously severe cases. Despite a considerable volume of clinical and research publications in the past 25 years, which generally point towards an organic basis to the condition, the PCS seems to remain largely overlooked or under-diagnosed in this country. This paper presents a summary of the history of medical research and controversy relating to concussion and the PCS. Evidence in support of the organic aetiology of the PCS is summarised.


Environmental Isolation of Candida auris from the Coastal Wetlands of Andaman Islands, India.
Candida auris is a multidrug resistant pathogen that presents a serious global threat to human health. As C. auris is a newly emerged pathogen, several questions regarding its ecological niche remain unexplored. While species closely related to C. auris have been detected in different environmental habitats, little is known about the natural habitat(s) of C. auris Here, we explored the virgin habitats around the very isolated Andaman Islands in the Indian Ocean for evidence of C. auris We sampled coastal wetlands, including rocky shores, sandy beaches, tidal marshes, and mangrove swamps, around the Andaman group of the Andaman & Nicobar Islands, Union Territory, in India. Forty-eight samples of sediment soil and seawater were collected from eight sampling sites representing the heterogeneity of intertidal habitats across the east and west coast of South Andaman district. C. auris was isolated from two of the eight sampling sites, a salt marsh and a sandy beach. Interestingly, both multidrug-susceptible and multidrug-resistant C. auris isolates were found in the sample. Whole-genome sequencing analysis clustered the C. auris isolates into clade I, showing close similarity to other isolates from South Asia. Isolation of C. auris from the tropical coastal environment suggests its association with the marine ecosystem. The fact that viable C. auris was detected in the marine habitat confirms C. auris survival in harsh wetlands. However, the ecological significance of C. auris in salt marsh wetland and sandy beaches to human infections remains to be explored.IMPORTANCECandida auris is a recently emerged multidrug-resistant fungal pathogen capable of causing severe infections in hospitalized patients. Despite its recognition as a human pathogen a decade ago, so far the natural ecological niche(s) of C. auris remains enigmatic. A previous hypothesis suggested that C. auris might be native to wetlands, that its emergence as a human pathogen might have been linked to global warming effects on wetlands, and that its enrichment in that ecological niche was favored by the ability of C. auris for thermal tolerance and salinity tolerance. To understand the mystery of environmental niches of C. auris, we explored the coastal wetland habitat around the very isolated Andaman Islands in the Indian Ocean. C. auris was isolated from the virgin habitats of salt marsh area with no human activity and from a sandy beach. C. auris isolation from the marine wetlands suggests that prior to its recognition as a human pathogen, it existed as an environmental fungus.


Thrombolytic therapy in cerebral venous sinus thrombosis.
The use of thrombolytic agents to rapidly lyse the clot has emerged as a therapeutic modality, in concert with interventional neuroradiologic approaches to deliver the agent locally at the site of thrombosis. There are no randomized, double blind, placebo, controlled trials to support thrombolysis as a first line therapy in patients with cerebral venous sinus thrombosis compared to standard therapy using anticoagulation with weight based dose adjusted unfractionated Heparin. Numerous case reports and a single non randomized trial have shown that it is comparatively safe and may rescue patients who are deteriorating despite anticoagulation with unfractionated Heparin. Consideration must be given to the use of thrombolysis in this group. This is an approach that must be restricted to centers with considerable experience in neurointerventional therapy.


Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression.
Endometriosis, classified as the presence of endometrial cells in ectopic sites, is a debilitating disease causing pain and infertility in approximately 10% of women of reproductive age. It is associated with the aberrant expression of extracellular matrix (ECM) components and their receptors, integrins. We analysed the expression of integrins in stromal cells derived from peritoneal, ovarian and deeply infiltrating endometriotic lesions and from endometrium from women with and without endometriosis in vitro, using quantitative immunocytochemistry. The adhesive and proliferative capacity of each of the cell types in response to ECM components was assessed by in vitro assays of cell attachment and DNA synthesis. We demonstrate that eutopic and ectopic endometrial stromal cells from women with endometriosis exhibit an aberrant integrin profile in vitro compared with stromal cells derived from healthy controls. In addition, the former display increased adhesion and proliferative capacity in response to specific ECM components. We propose that the increased adhesive and proliferative potential of cells from endometriotic lesions may be a key feature in the pathogenesis of endometriosis. Furthermore, the elevated responsiveness of eutopic cells from women with endometriosis may contribute to the predisposition of some women to the disease.


Behavior in early adolescence and risk of human papillomavirus infection as a young adult: results from a population-based study.
The goal of this study was to determine the utility of a risk factor-based approach to human papillomavirus catch-up vaccination. Data from waves I and III of the National Longitudinal Study of Adolescent Health were examined to determine the association between adolescent characteristics and future human papillomavirus infection. Analysis was restricted to 3181 female subjects who were >12 years of age when risk factors were assessed in wave I (1994-1995) and who underwent human papillomavirus testing as young adults in wave III (2001-2002). The main outcome of interest was a positive test result for >or=1 of 4 human papillomavirus types (human papillomavirus-6, -11, -16, or -18) targeted by the human papillomavirus vaccine currently available in the United States. Separate analyses were performed for sexually active and virginal adolescents. Poststratification sampling weights were used to generate nationally representative estimates. Although nearly one half (43%) of the female adolescents were sexually active in wave I, adolescent sexual activity status was not associated with future detection of vaccine-specific human papillomavirus infection. Furthermore, for both virginal and sexually active adolescents, none of the assessed risk factors was associated with increased odds of future vaccine-specific human papillomavirus infection in multivariate models. Similar results were obtained when all high-risk human papillomavirus types were assessed as the outcome measure. Behavioral risk factors assessed during adolescence are inadequate predictors of future infection with vaccine-type human papillomavirus. A risk factor-based approach to human papillomavirus catch-up vaccination is unlikely to be an effective implementation strategy.


Limited proteolysis of type I collagen at hyperreactive sites by class I and II Clostridium histolyticum collagenases: complementary digestion patterns.
The initial proteolytic events in the hydrolysis of rat tendon type I collagen by the class I and II collagenases from Clostridium histolyticum have been investigated at 15 degrees C. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis has been used to detect the initial cleavage fragments of both the alpha 1(I) and alpha 2 chains, which migrate at different rates in the buffer system employed. Experiments with the class I collagenases indicate that the first cleavage occurs across all three chains of the triple helix close to the C-terminus to produce fragments whose alpha chains have molecular weights of approximately 88,000. The second cleavage occurs near the N-terminus to reduce the molecular weight of the alpha chains to 80,000. Initial proteolysis by the class II collagenases occurs across all three chains at a site in the interior of the collagen triple helix to give N- and C-terminal fragments with alpha-chain molecular weights of 35,000 and 62,000, respectively. The C-terminal fragment is subsequently cleaved to give fragments with alpha-chain molecular weights of 59,000. These results indicate that type I collagen is degraded at several hyperreactive sites by these enzymes. Thus, initial proteolysis by these bacterial collagenases occurs at specific sites, much like the mammalian collagenases. These results with the individual clostridial collagenases provide an explanation for earlier data which indicated that collagen is degraded sequentially from the ends by a crude clostridial collagenase preparation.


Letter to the Editor.
Neuroendocrine tumors (NETs) are uncommon type of cancers, also known as APUD (amine precursor uptake decarboxylation) tumors, which are becoming increasingly prevalent. Alkaline phosphatase (ALP) is a poor prognosis factor in a number of hepatic diseases. However, its distribution and prognostic value in primary hepatic neuroendocrine tumors (PHNETs) are still not clear. In this study, our aim is to investigate the correlations between ALP and clinicopathological features and prognostic factors of PHNETs. The clinical data of 22 patients with PHNETs were retrospectively reviewed to investigate whether ALP affects the prognosis of PHNETs. In this study, ALP is correlated to γ-glutamyl transpeptidase (GGT; p = 0.002) and the tumor location in the liver (p = 0.007), and increased levels of ALP had poor effects on overall survival (p = 0.006) and progression-free survival (p = 0.022). ALP was identified as an independent prognostic factor for overall survival of PHNETs.


Synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups.
In this paper, a novel synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups is presented. Anionically activated trifluoromethyl groups react with secondary amines under aqueous conditions to afford tertiary amides. The mechanism involves initial elimination of hydrogen fluoride by an E1cB mechanism to afford an electrophilic quinone methide- or azafulvene-type intermediate that reacts with secondary amines under aqueous conditions to afford the tertiary amide in good yield (up to 99%).


Association of Fried Food Intake with Gastric Cancer Risk: A Systemic Review and Meta-Analysis of Case-Control Studies.
Gastric cancer is one of the most prevalent cancers in Asia, and has a significant global incidence. However, the impact of fried food consumption on gastric cancer risk remains uncertain, mainly due to the limited number of participants in previous studies. To address this knowledge gap, we aimed to examine the association between fried food intake and gastric cancer incidence through a comprehensive meta-analysis. We conducted a thorough search across multiple databases, including PubMed, EMBASE, Google Scholar, Cochrane Library, China National Knowledge Infrastructure (CNKI), Korean Information Service System (KISS), and Research Information Service System (RISS), to collect studies. The newly analyzed results of the Korean Genome and Epidemiology Study (KoGES) findings were added. We assessed integrated odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) from the selected studies using Cochrane RevMan 5.0 for the meta-analysis. The quality of the studies included in the meta-analysis was assessed using the Study Quality Assessment Tool of the National Heart, Lung, and Blood Institute (NHLBI). We included 18 studies in the analysis, which compared the impact of fried food intake in gastric cancer patients (n = 5739) and healthy adults (control, n = 70,933). There was a significant positive association between gastric cancer risk and fried food intake (OR = 1.52, 95% CI = 1.23-1.87, I2 = 76%, p = 0.0001). The relationship was found to be significant in both non-East Asians (OR = 1.48, 95% CI = 1.18-1.85, I2 = 31%, p = 0.0006) and East Asians (OR = 1.54, 95% CI = 1.14-2.08, I2 = 83%, p = 0.005). In conclusion, this meta-analysis supports the notion that fried food intake is associated with an increased risk of gastric cancer in both non-Asians and Asians. Promoting a reduction in fried food consumption as a measure against gastric cancer risk is recommended.


Density nonlinearities in field theories for a toy model of fluctuating nonlinear hydrodynamics of supercooled liquids.
We study a zero-dimensional version of the fluctuating nonlinear hydrodynamics (FNH) of supercooled liquids originally investigated by Das and Mazenko (DM) [Shankar P. Das and Gene F. Mazenko Phys. Rev. A 34, 2265 (1986)]. The time-dependent density-like and momentum-like variables are introduced with no spatial degrees of freedom in this toy model. The structure of nonlinearities takes the similar form to the original FNH, which allows one to study in a simpler setting the issues raised recently regarding the field theoretical approaches to glass forming liquids. We study the effects of density nonlinearities on the time evolution of correlation and response functions by developing field theoretic formulations in two different ways: first by following the original prescription of DM and then by constructing a dynamical action which possesses a linear time-reversal symmetry as proposed recently. We show explicitly that, at the one-loop order of the perturbation theory, the DM-type field theory does not support a sharp ergodic-nonergodic transition, while the other admits one. The simple nature of the toy model in the DM formulation allows us to develop numerical solutions to a complete set of coupled dynamical equations for the correlation and response functions at the one-loop order.


A KCNQ1 V205M missense mutation causes a high rate of long QT syndrome in a First Nations community of northern British Columbia: a community-based approach to understanding the impact.
Hereditary long QT syndrome is named for a prolonged QT interval reflecting predisposition to ventricular arrhythmias and sudden death. A high rate in a remote, northern Canadian First Nations community was brought to attention. Two severely affected index cases and 122 relatives were ascertained using community-based participatory research principles. Genetic sequencing of five known genes responsible for long QT syndrome was carried out on the index cases, leading to the identification of a novel missense mutation. Functional properties of the identified mutation were studied in transfected mouse ltk- cells using whole cell patch clamp techniques. Corrected QT interval measurements were obtained from participants and subsequent genotyping of relatives was carried out. In the two index cases, a novel missense mutation (V205M) was identified in the S3 transmembrane helix of KvLQT1, the pore forming domain of the IKs channel complex. In transfected mouse ltk-cells the V205M mutation suppressed IKs by causing a dramatic depolarizing shift in activation voltage coupled with acceleration of channel deactivation. Twenty-two mutation carriers had a significantly higher mean corrected QT interval than noncarriers (465 +/- 28 milliseconds vs. 434 +/- 26 milliseconds, P < 0.0001); however, 30% of carriers had a corrected QT interval below 440 milliseconds. A novel KCNQ1 mutation in this founder population likely confers increased susceptibility to arrhythmias because of decreased IKs current. Even with a common mutation within a relatively homogenous population, clinical expression remains variable, exemplifying the multifactorial nature of long QT syndrome, and supporting the difficulty of definitive diagnosis without genetic testing. A community participatory approach enabled a comprehensive evaluation of the impact.


Metabolic and structural rearrangement during dark-induced autophagy in soybean (Glycine max L.) nodules: an electron microscopy and 31P and 13C nuclear magnetic resonance study.
The effects of dark-induced stress on the evolution of the soluble metabolites present in senescent soybean (Glycine max L.) nodules were analysed in vitro using (13)C- and (31)P-NMR spectroscopy. Sucrose and trehalose were the predominant soluble storage carbons. During dark-induced stress, a decline in sugars and some key glycolytic metabolites was observed. Whereas 84% of the sucrose disappeared, only one-half of the trehalose was utilised. This decline coincides with the depletion of Gln, Asn, Ala and with an accumulation of ureides, which reflect a huge reduction of the N(2) fixation. Concomitantly, phosphodiesters and compounds like P-choline, a good marker of membrane phospholipids hydrolysis and cell autophagy, accumulated in the nodules. An autophagic process was confirmed by the decrease in cell fatty acid content. In addition, a slight increase in unsaturated fatty acids (oleic and linoleic acids) was observed, probably as a response to peroxidation reactions. Electron microscopy analysis revealed that, despite membranes dismantling, most of the bacteroids seem to be structurally intact. Taken together, our results show that the carbohydrate starvation induced in soybean by dark stress triggers a profound metabolic and structural rearrangement in the infected cells of soybean nodule which is representative of symbiotic cessation.


Detection of inducible nitric oxide synthase- and nitrotyrosine-positive cells in the lesions of pericarditis induced by porcine enterovirus serotype 3 infection.
The expression of inducible nitric oxide synthase (iNOS), an enzyme that produces nitric oxide, was examined in the hearts of pigs infected with porcine enterovirus serotype 3 (PEV3). Piglets orally infected with PEV3 developed tremors and paralysis 3-7 days post-infection. Affected animals had pericarditis and myocarditis. There were fibrin and inflammatory cell infiltrates (macrophages and neutrophils) in the pericardial sac and myocardium. Immunohistochemically, the majority of inflammatory cells in the pericardial sac were positive for iNOS and nitrotyrosine, an end product of nitric oxide. These results suggest that iNOS is upregulated in the pericardial lesion, and that increased nitric oxide production plays an important role in the development of PEV3-induced pericarditis and myocarditis.


Depression and Risk for Problem Drinking in Latino Migrant Day Laborers.
Given the structural vulnerability of Latino migrant day laborers (LMDLs) to unstable and poorly paying work, harsh living conditions and frequent inability to support or even visit families in country of origin, psychological distress is a common response and one frequently implicated in risky outcomes such as problem drinking. The purpose of this study was to examine the relation of three different forms of psychological distress to problem drinking in LMDLs: depression, anxiety, and desesperación, the latter a popular Latino culture-based idiom of psychological distress. A cross sectional survey of 344 LMDLs was conducted in the San Francisco Bay Area from January to June of 2014. Independent contributions of depression, anxiety, and desesperación in explaining problem drinking as measured by a modified version of the AUDIT, were assessed using multiple linear regression analysis. Depression was significantly associated with risk for problem drinking while other forms of psychological distress were not. Conclusion/Importance: Findings provide stronger empirical support for the association between depression and problem drinking, a long suspected but under-demonstrated relationship in the literature on LMDLs. Implications for preventing problem drinking as well as mitigating psychological distress more generally for LMDLs are discussed.


Postoperative infections of the thoracic and lumbar spine: a review of 18 cases.
We retrospectively reviewed 18 consecutive patients (age range, 19-81 years; average age, 55 years) with postoperative infections of the spine. Postdiscectomy-laminectomy infections confined to the disc space (n = 2) were treated with percutaneous transpedicle drainage. Open débridement was performed in patients with an epidural or paraspinal abscess (n = 3). Infections after posterior instrumentation that manifested during the first postoperative month were treated with single (n = 3) or multiple débridements and delayed closure (n = 7), with preservation of instrumentation. Infections that presented more than 9 months after the initial operation (n = 3) were treated with open débridement and removal of instrumentation. The minimum followup was 1 year (mean 2 years, range, 1-4 years). Infections in 17 of the 18 patients resolved effectively and one patient with metastatic cancer died of sepsis. Transpedicle drainage resulted in immediate relief of back pain. Instrumentation can be retained safely in patients with infections that manifest during the first month after implantation. Single surgical débridement is effective in selected cases. After repeated débridements, the presence of healthy granulation tissue in the wound and decreasing C-reactive protein activity were associated with safe and effective wound closure. Despite radiographic evidence of hardware loosening in infections manifested more than 9 months after implantation, we removed hardware without destabilizing the spine.


Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs.
Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites. Cumulative or overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either directly or indirectly after their biotransformation. ALF is the result of massive death of hepatocytes induced by oxidative stress. There is an increased interest in the use of natural dietary products as nutritional supplements and/or medications to prevent or cure many diseases. The therapeutic activity of natural products may be associated with their antioxidant capacity, although additional mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary antioxidants such as flavonoids, betalains and carotenoids play a preventive role against OTC analgesics-induced ALF. In this review, we will summarize the pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its prevention and therapy.


Consistent habitat preference underpins the geographically divergent autumn migration of individual Mongolian common shelducks.
While many avian populations follow narrow, well-defined "migratory corridors," individuals from other populations undertake highly divergent individual migration routes, using widely dispersed stopover sites en route between breeding and wintering areas, although the reasons for these differences are rarely investigated. We combined individual GPS-tracked migration data from Mongolian-breeding common shelduck Tadorna tadorna and remote sensing datasets, to investigate habitat selection at inland stopover sites used by these birds during dispersed autumn migration, to explain their divergent migration patterns. We used generalized linear mixed models to investigate population-level resource selection, and generalized linear models to investigate stopover-site-level resource selection. The population-level model showed that water recurrence had the strongest positive effect on determining birds' occupancy at staging sites, while cultivated land and grassland land cover type had strongest negative effects; effects of other land cover types were negative but weaker, particularly effects of water seasonality and presence of a human footprint, which were positive but weak or non-significant, respectively. Although stopover-site-level models showed variable resource selection patterns, the variance partitioning and cross-prediction AUC scores corroborated high inter-individual consistency in habitat selection at inland stopover sites during the dispersed autumn migration. These results suggest that the geographically widespread distribution (and generally rarity) of suitable habitats explained the spatially divergent autumn migrations of Mongolian breeding common shelduck, rather than the species showing flexible autumn staging habitat occupancy.


Differential Gene Expression Landscape of Co-Existing Cervical Pre-Cancer Lesions Using RNA-seq.
Genetic changes occurring in different stages of pre-cancer lesions reflect causal events initiating and promoting the progression to cancer. Co-existing pre-cancerous lesions including low- and high-grade squamous intraepithelial lesion (LGSIL and HGSIL), and adjacent "normal" cervical epithelium from six formalin-fixed paraffin-embedded samples were selected. Tissues from these 18 samples were isolated using laser-capture microdissection, RNA was extracted and sequenced. RNA-sequencing generated 2.4 billion raw reads in 18 samples, of which ~50.1% mapped to known and annotated genes in the human genome. There were 40 genes up-regulated and 3 down-regulated (normal to LGSIL) in at least one-third of the sample pairs (same direction and FDR p < 0.05) including S100A7 and KLK6. Previous studies have shown that S110A7 and KLK7 are up-regulated in several other cancers, whereas CCL18, CFTR, and SLC6A14, also differentially expressed in two samples, are up-regulated specifically in cervical cancer. These differentially expressed genes in normal to LGSIL progression were enriched in pathways related to epithelial cell differentiation, keratinocyte differentiation, peptidase, and extracellular activities. In progression from LGSIL to HGSIL, two genes were up-regulated and five down-regulated in at least two samples. Further investigations using co-existing samples, which account for all internal confounders, will provide insights to better understand progression of cervical pre-cancer.


Dual brain stimulation enhances interpersonal learning through spontaneous movement synchrony.
Social interactive learning denotes the ability to acquire new information from a conspecific-a prerequisite for cultural evolution and survival. As inspired by recent neurophysiological research, here we tested whether social interactive learning can be augmented by exogenously synchronizing oscillatory brain activity across an instructor and a learner engaged in a naturalistic song-learning task. We used a dual brain stimulation protocol entailing the trans-cranial delivery of synchronized electric currents in two individuals simultaneously. When we stimulated inferior frontal brain regions, with 6 Hz alternating currents being in-phase between the instructor and the learner, the dyad exhibited spontaneous and synchronized body movement. Remarkably, this stimulation also led to enhanced learning performance. These effects were both phase- and frequency-specific: 6 Hz anti-phase stimulation or 10 Hz in-phase stimulation, did not yield comparable results. Furthermore, a mediation analysis disclosed that interpersonal movement synchrony acted as a partial mediator of the effect of dual brain stimulation on learning performance, i.e. possibly facilitating the effect of dual brain stimulation on learning. Our results provide a causal demonstration that inter-brain synchronization is a sufficient condition to improve real-time information transfer between pairs of individuals.


[Relation between Mg2+ activation and AMP inhibition of fructose-1,6-diphosphatase from rabbit skeletal muscles].
It was shown that AMP, an allosteric inhibitor of fructose-1.6-bisphosphatase, decreases the apparent affinity of the enzyme for the activating cation, Mg2+, which is accompanied by a decrease of the kinetic cooperativity between the Mg2+-binding sites. In its turn, the Mg2+ increase diminishes the enzyme sensitivity to the inhibiting effect of AMP and decreases the cooperativity of the inhibitor binding. The heterotropic interactions between the allosteric inhibitor and activator binding centers are consistent with the predictions of the Monod-Wyman-Changeux model which involves two conformational states of the enzyme (of which one is catalytically inactive) differing in their affinity for the ligands. An increase in pH from 7.4 to 9.0 increases the enzyme affinity for Mg2+ and causes an equilibrium shift towards the catalytically active state of the enzyme.


Reduction in N-Desmethylclozapine Level Is Determined by Daily Dose But Not Serum Concentration of Valproic Acid-Indications of a Presystemic Interaction Mechanism.
Valproic acid (VPA) is frequently used together with clozapine (CLZ) as mood-stabilizer or for the prevention of seizures in patients with psychotic disorders. VPA is known to reduce levels of the pharmacologically active CLZ-metabolite N-desmethylclozapine (N-DMC), but factors determining the degree of this interaction are unknown. Here, we investigated the relationship between VPA dose and serum concentration on N-DMC levels in a large patient population adjusting for sex, age, and smoking habits as covariates. A total of 763 patients with steady-state serum concentrations of CLZ and N-DMC concurrently using VPA (cases, n = 76) or no interacting drugs (controls, n = 687) were retrospectively included from a therapeutic drug monitoring service at Diakonhjemmet Hospital, Oslo, between March 2005 and December 2016. In addition to information about prescribed doses, age, sex, smoking habits, and use of other interacting drugs were obtained. The effects of VPA dose and serum concentration on dose-adjusted N-DMC levels were evaluated by univariate correlation and multivariate linear mixed-model analyses adjusting for covariates. The dose-adjusted N-DMC levels were approximately 38% lower in VPA users (cases) versus nonusers (controls) (P < 0.001). Within the VPA cases, a negatively correlation between VPA dose and dose-adjusted N-DMC levels was observed with an estimated reduction of 1.42% per 100-mg VPA dose (P = 0.033) after adjusting for sex, age, and smoking. By contrast, there was no correlation between VPA serum concentration and dose-adjusted N-DMC levels (P = 0.873). The study shows that VPA dose, not concentration, is of relevance for the degree of reduction in N-DMC level in clozapine-treated patients. Presystemic induction of UGT enzymes or efflux transporters might underlie the reduction in N-DMC level during concurrent use of VPA. Our findings indicate that a VPA daily dose of 1500 mg or higher provides a further 21% reduction in N-DMC concentration. This is likely a relevant change in the exposure of this active metabolite where low levels are associated with implications of CLZ therapy.


Intratumoral immune triads are required for adoptive T cell therapy-mediated elimination of solid tumors.
Tumor-reactive CD8 T cells found in cancer patients are frequently dysfunctional, unable to halt tumor growth. Adoptive T cell transfer (ACT), the administration of large numbers of in vitro-generated cytolytic tumor-reactive CD8 T cells, is an important cancer immune therapy being pursued. However, a limitation of ACT is that transferred CD8 T cells often rapidly lose effector function, and despite exciting results in certain malignancies, few ACT clinical trials have shown responses in solid tumors. Here, we developed preclinical cancer mouse models to investigate if and how tumor-specific CD4 T cells can be enlisted to overcome CD8 T cell dysfunction in the setting of ACT. In situ confocal microscopy of color-coded cancer cells, tumor-specific CD8 and CD4 T cells, and antigen presenting cells (APC), combined with functional studies, revealed that the spatial positioning and interactions of CD8 and CD4 T cells, but not their numbers, dictates ACT efficacy and anti-tumor responses. We uncover a new role of antigen-specific CD4 T cells in addition to the known requirement for CD4 T cells during priming/activation of naïve CD8 T cells. CD4 T cells must co-engage with CD8 T cells and APC cross-presenting CD8- and CD4-tumor antigens during the effector phase, forming a three-cell-cluster (triad), to license CD8 T cell cytotoxicity and mediate cancer cell elimination. Triad formation transcriptionally and epigenetically reprogram CD8 T cells, prevent T cell dysfunction/exhaustion, and ultimately lead to the elimination of large established tumors and confer long-term protection from recurrence. When intratumoral triad formation was disrupted, adoptively transferred CD8 T cells could not be reprogrammed, and tumors progressed despite equal numbers of tumor-infiltrating CD8 and CD4 T cells. Strikingly, the formation of CD4 T cell::CD8 T cell::APC triads in tumors of patients with lung cancers treated with immune checkpoint blockade was associated with clinical responses, but not CD4::APC dyads or overall numbers of CD8 or CD4 T cells, demonstrating the importance of triads in non-ACT settings in humans. Our work uncovers intratumoral triads as a key requirement for anti-tumor immunity and a new role for CD4 T cells in CD8 T cell cytotoxicity and cancer cell eradication.


Immunologic and immunohistochemical study of familial amyloid polyneuropathy.
Amyloid fibril protein was purified from postmortem organs of patients with familial amyloid polyneuropathy. In immunodiffusion tests, the protein reacted with antihuman prealbumin antibody but not with antihuman retinol-binding protein or antihuman immunoglobulin G (IgG). In immunoelectrophoresis, the amyloid fibril protein gave a single line with a slightly faster mobility than prealbumin. Immunohistochemical analysis, using fluorescent and peroxidase-antiperoxidase methods, showed that the amyloid deposits contained antigenic determinants of human retinol-binding protein and IgG but not prealbumin.


[Gingival hyperplasia and serous papules due to cyclosporin treatment].
After 3 months of immunosuppressive treatment with cyclosporin because of a focal segmental glomerulosclerosis, a 13-year-old female developed marked gingival hyperplasia, hypertrichosis of the arms and papulo-vesicular skin lesions on the left leg. Histological and immunohistological examinations of the gingivae showed hyperplasia of the mucosa with perivascular infiltrates of plasma and B cells in the submucosa. The lesions on the leg revealed signs of cutaneous vascular inflammation with eosinophils, but there was no evidence of leucocytoclastic vasculitis. Ten months after discontinuation of cyclosporin, the lesions had nearly regressed. The patient's renal function deteriorated progressively to the point of terminal insufficiency.


Distribution of CCR5-Delta32, CCR5 promoter 59029 A/G, CCR2-64I and SDF1-3'A genetic polymorphisms in HIV-1 infected and uninfected patients in the west region of Cameroon.
Genetic variants of the genes encoding human immunodeficiency virus-1 (HIV-1) co-receptors and their ligands, like CC-chemokine receptor 5 delta 32 mutation (CCR5-Delta32), CCR5 promoter A/G (Adenine/Guanine), CC-chemokine receptor 2 mutation 64 isoleucine (CCR2-64I) and the stromal cell-derived factor 3'A mutation (SDF1-3'A), are involved in the susceptibility to HIV-1 infection and progression. The prevalence of these mutations varies by region. However, little is known about their distribution in the population of Dschang, located in the west region of Cameroon. The prevalence of HIV in the west region of Cameroon is lower than elsewhere in Cameroon. The objectives of this study were to determine the distribution of four AIDS Related Gene (ARG) variants in HIV-infected and non-infected population of Cameroon especially in the west region and to estimate the contribution of these variants to the susceptibility or resistance to HIV infection. We also aimed to evaluate the effectiveness of genotyping using dried blood spot (DBS) samples. A total of 179 participants were recruited from two hospitals in Dschang in the west region of Cameroon. Their genotypes for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3'A were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphisms. A total of 179 participants were enrolled in the study. Among them, 32 (17.9%) were HIV positive and 147 (82.1%) were HIV negative. The allelic frequencies of these genes were: 0%, 49.72%, 17.6% and 100% respectively for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3'A. No individual was found to carry the CCR5-Delta 32 mutation. All participants recruited were heterozygous for the SDF1-3'A allele. Our data suggest that the CCR5-Delta32 cannot account for the protection as it was completely absent in our population. SDF1-3'A variants, may be in association with other polymorphisms, may account for the overall protection from HIV-1 infection in participants recruited as everyone carries this allele. The CCR5 promoter 59029 G/G genotype may be associated with the risk for HIV-1 infection in this population, while the CCR2-64I (A/A genotype) may account for the protection against HIV infection. The results of genotyping from fresh blood and DBS were comparable.


Behavioral effects of urotensin-II centrally administered in mice.
Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.


Relationship between team identification and trait aggression: a replication.
Research yielded no significant relationship between sport fandom and trait aggression. The current study replicated previous efforts using the Buss-Perry Aggression Questionnaire, an updated version of the Buss-Durkee Hostility Inventory. In contrast to past work, the current study did yield a significant relationship between fandom and aggression for men.


Predictors of improvement in semen parameters after varicocelectomy for male subfertility: A prospective study.
We aim to predict results of varicocelectomy on sperm density and progressive motility using preoperative clinical, laboratory and radiological data and to propose cut-off values for significant parameters. This prospective study was carried out between July 2011 and June 2014. We included 123 patients in our study. They were diagnosed with primary infertility with varicocele, were scheduled for varicocelectomy, and completed their follow-up. We excluded patients with azoospermia, total necrospermia, recurrent varicocele, and pituitary hormonal abnormalities. Varicocele was diagnosed and graded by physical examination and colour Doppler ultrasound. Semen analyses were completed preoperatively and 6 months postoperatively. Microscopic subinguinal varicocelectomy was done in all cases. Patient demographics, pre- and postoperative clinical data (varicocele grade and semen parameters) were statistically analyzed. The mean ± standard deviation of age, body mass index, and subfertility duration was 28.3 ± 7.4 years, 29.1 ± 2.7 kg/m(2), and 21.9 ± 7.1 months, respectively. About 53% of our patients (n = 66) had bilateral varicocele, and unilateral disease was found in the other 57 (46.3%) cases. Varicocele grade I was diagnosed in 42 (34.1%) patients, while the other 81 (65.9%) patients had grade II or III. Higher grades of varicocele, preoperative total testosterone level, sperm density, and progressive motility had a statistically significant impact on the outcome of varicocelectomy in univariate testing. Multivariate logistic analysis revealed that grade of preoperative varicocele (95% confidence interval [CI] 5.6-6.3, p = 0.007) and sperm density (95% CI 2.7-1.6, p = 0.0035), and progressive motility (95% CI 1.1-2.3, p = 0.0123) are independent predictors of semen parameters improvement after varicocelectomy. The grade of the varicocele, sperm density, and progressive motility are major predictors of outcome in varicocelectomy. Cut-off values of >8 million/mL and >18% for sperm density and progressive motility, respectively, in men with varicocele grade II or III, indicate a successful outcome.


Psychiatric diseases presenting as infectious diseases.
Although many psychiatric diseases have somatic manifestations, some focus on fears or delusions of infection. When a patient with a psychiatric basis for an apparent infection presents to an infectious disease physician, the physician may find the problem confusing, amusing, and ultimately frustrating until the psychiatric basis for disease is recognized. Some of these psychiatric disorders can be treated and controlled with medication and psychotherapy, although patients may resist psychiatric referral. This article reviews examples of psychiatric disorders in patients who present to the infectious disease physician, including factitious infection, malingering, obsessive compulsive disorder, phobias, veneroneuroses, somatization disorders, and delusional infection. The role that physicians play in amplifying these disorders is reviewed. Strategies for referral to psychiatric services are also discussed. Patients with a psychiatric disease are seen in infectious disease practices more commonly than physicians realize.


Effects of neonatal treatment with two phytoestrogens on male rat sexual behavior and partner preference.
The aim of this work was to compare the effect of neonatal treatment with the phytoestrogens coumestrol (COU) and genistein (GEN), administered in equimolecular doses, on the sexual behavior and partner preference of male rats. Four groups of male rats were injected daily from day 1 to 5 with 150 µg of GEN, an equivalent amount of COU, 1 µg of β-estradiol 3-benzoato (EB), or olive oil (VEH) (control). A fifth group remained intact. In the GEN group, intromission and ejaculation latencies decreased, whereas ejaculatory frequency increased. Contrasting results were observed in COU males. EB males could not ejaculate and their mount and intromission latencies increased significantly. To determine sexual-partner preferences, a multiple partner preference arena was used and two types of tests were performed, the first one without allowing contact test (CT) with the stimulus animals, followed by a CT. COU and GEN groups did not show preference for any stimulus animal, whereas the EB males preferred the expert male. When CT with the stimulus animals was allowed, GEN-males preferred the receptive female, unlike the COU and EB groups. It is concluded that neonatal treatment with COU and GEN induced opposite effects, the effects of COU being more estrogenic.